Prognostic value of the ferroptosis-related gene SLC2A3 in gastric cancer and related immune mechanisms

Lei, Lin; Que, Renye; Wang, Jian; Zhu, Yi; Liu, Xiaolin

doi:10.3389/fgene.2022.919313

Cited by 12 publications

(4 citation statements)

References 31 publications

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“…SLC2A3 may affect the immune response [ 17 ]. GSEA revealed that IL6/JAK/STAT3 signaling and interferon-γ response pathways were enriched in the upregulated genes in HNSC ( Figures 6a, 6b ).…”

Section: Resultsmentioning

confidence: 99%

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Chai

Zhang

et al. 2023

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SLC2A3 is an important member of the glucose transporter superfamily. It has been recently suggested that upregulation of SLC2A3 is associated with poor survival and acts as a prognostic marker in a variety of tumors. Unfortunately, the prognostic role of SLC2A3 in head and neck squamous cell carcinoma (HNSC) is less known. In the present study, we analyzed SLC2A3 expression in HNSC and its correlation with prognosis using TCGA and GEO databases. The results showed that SLC2A3 mRNA expression was higher in HNSC compared with adjacent normal tissues, which was validated with our 9 pairs of HNSC specimens. Moreover, high SLC2A3 expression predicted poor prognosis in HNSC patients. Mechanistically, GSEA revealed that high expression of SLC2A3 was enriched in epithelial-mesenchymal transition (EMT) and NF-κB signaling. In HNSC cell lines, SLC2A3 knockdown inhibited cell proliferation and migration. In addition, NF-κB P65 and EMT-related gene expression was suppressed upon SLC2A3 knockdown, indicating that SLC2A3 may play a preeminent role in the progression of HNSC through the NF-κB/EMT axis. Meanwhile, the expression of SLC2A3 was negatively correlated with immune cells, suggesting that SLC2A3 may be involved in the immune response in HNSC. The correlation between SLC2A3 expression and drug sensitivity was further assessed. In conclusion, our study demonstrated that SLC2A3 could predict the prognosis of HNSC patients and mediate the progression of HNSC via the NF-κB/EMT axis and immune responses.

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Section: Resultsmentioning

confidence: 99%

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Chai

Zhang

et al. 2023

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“…The results of this study and the reports from the literature indicate that the upregulated SLC2A3 is a ferroptosis marker involved in transmembrane glucose transport, and current studies on SLC2A3 have focused on cancer. Lin et al (2022) found that overexpression of SLC2A3 in tumor tissues is associated with poor prognosis in patients with gastric cancer. By immunohistochemical staining, SLC2A3 expression was found to be higher in colorectal cancer tissues than in adjacent nontumor colorectal mucosal tissues, and SLC2A3 could mediate the immune response by regulating EMT and PD-L1 (Gao et al, 2021).…”

Section: Discussionmentioning

confidence: 96%

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Pan

et al. 2023

Front. Pharmacol.

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Introduction: Periodontitis is a chronic inflammatory oral disease that destroys soft and hard periodontal support tissues. Multiple cell death modes including apoptosis, necroptosis, pyroptosis, and ferroptosis play a crucial role in the pathogenicity of inflammatory diseases. This study aimed to identify genes associated with ferroptosis, necroptosis, and pyroptosis in different cells present in the periodontium of periodontitis patients.Methods: Gingival tissues’ mRNA sequencing dataset GSE173078 of 12 healthy control and 12 periodontitis patients’ and the microarray dataset GSE10334 of 63 healthy controls and 64 periodontitis patients’ were obtained from Gene Expression Omnibus (GEO) database. A total of 910 differentially expressed genes (DEGs) obtained in GSE173078 were intersected with necroptosis, pyroptosis, and ferroptosis-related genes to obtain the differential genes associated with cell death (DCDEGs), and the expression levels of 21 differential genes associated with cell death were verified with dataset GSE10334.Results: Bioinformatic analysis revealed 21 differential genes associated with cell death attributed to ferroptosis, pyroptosis, and necroptosis in periodontitis patients compared with healthy controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that 21 differential genes associated with cell death were related to various cellular and immunological pathways including inflammatory responses, necroptosis, and osteoclast differentiation. Additionally, the single-cell RNA (scRNA) sequencing data GSE171213 of 4 healthy controls and 5 periodontitis patients’ periodontal tissue was analyzed to obtain cell clustering and cell types attributed to differential genes associated with cell death. We found that among 21 DCDEGs, SLC2A3, FPR2, TREM1, and IL1B were mainly upregulated in neutrophils present in the periodontium of periodontitis patients. Gene overlapping analysis revealed that IL-1B is related to necroptosis and pyroptosis, TREM1 and FPR2 are related to pyroptosis, and SLC2A3 is related to ferroptosis. Finally, we utilized the CIBERSORT algorithm to assess the association between DCDEGs and immune infiltration phenotypes, based on the gene expression profile of GSE10334. The results revealed that the upregulated SLC2A3, FPR2, TREM1, and IL1B were positively correlated with neutrophil infiltration in the periodontium.Discussion: The findings provide upregulated SLC2A3, FPR2, TREM1, and IL1B in neutrophils as a future research direction on the mode and mechanism of cell death in periodontitis and their role in disease pathogenicity.

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“…54 SLC2A3 exerts multiple biological functions in different cancers, including tumor EMT, ferroptosis, glycolytic reprogramming, drug resistance and immunity. [55][56][57][58][59] Immune cell infiltration analysis showed that SLC11A1 and SLC2A3 expression was positively correlated with the infiltration levels of neutrophils, macrophages, dendritic cells, CD4+ T cells and CD8+ T cells. Moreover, the higher the expression levels of SLC11A1 and SLC2A3, the lower the tumor purity.…”

Section: Discussionmentioning

confidence: 99%

“…Reportedly, SLC11A1 not only predicts the prognosis of colorectal cancer and hepatocellular carcinoma 52,53 but also serves as a stratification indicator for immunotherapy or chemotherapy in glioma patients 54 . SLC2A3 exerts multiple biological functions in different cancers, including tumor EMT, ferroptosis, glycolytic reprogramming, drug resistance and immunity 55–59 . Immune cell infiltration analysis showed that SLC11A1 and SLC2A3 expression was positively correlated with the infiltration levels of neutrophils, macrophages, dendritic cells, CD4+ T cells and CD8+ T cells.…”

Section: Discussionmentioning

confidence: 99%

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Wang,

Qiu

et al. 2024

The Journal of Gene Medicine

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BackgroundColon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients.MethodsWe first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression‐free survival (PFS) were assessed by Kaplan–Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues.ResultsWe established and validated a risk scoring model based on neutrophil‐related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high‐risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy.ConclusionsThe low‐risk group showed better OS and PFS than the high‐risk group in the neutrophil‐related gene‐based risk model. Patients in the high‐risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

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Prognostic value of the ferroptosis-related gene SLC2A3 in gastric cancer and related immune mechanisms

Cited by 12 publications

References 31 publications

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

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